JP6046041B2 - Devices, systems, and methods for neuromodulation therapy evaluation and feedback - Google Patents

Description

CROSS REFERENCE TO RELATED APPLICATION This application claims priority from the following pending applications:

  (A) US Provisional Patent Application No. 61 / 406,531 filed on Oct. 25, 2010

  (B) US Provisional Patent Application No. 61 / 528,108 filed on August 26, 2011

  (C) US Provisional Application No. 61 / 528,091 filed on August 26, 2011

  (D) US Provisional Patent Application No. 61 / 528,684, filed August 29, 2011

  In this specification, all of the above applications are incorporated by reference. Further, the components and features of the embodiments disclosed in the application and incorporated by reference may be combined with the various components and features disclosed and claimed herein.

  The present disclosure relates to neuromodulation therapy, and more particularly to devices, systems, and methods for providing evaluation and feedback to an operator of a device that provides neuromodulation therapy.

  The sympathetic nervous system (SNS) is a largely involuntary body control system typically associated with stress responses. SNS fibers innervate tissues in almost every organ system of the human body and can affect features such as pupil diameter, bowel motility, and urine output. Such regulation can have an adaptive utility in maintaining homeostasis or preparing the body for a rapid response to environmental factors. Chronic activation of SNS, however, is a common maladaptive response that can drive the progression of many disease states. In particular, excessive activation of the renal SNS has been experimentally identified in humans as a possible cause of the complex pathophysiology of hypertension, conditions of volume overload (such as heart failure), and progressive kidney disease Yes. For example, radiotracer dilution demonstrated increased renal norepinephrine (NE) spillover rates in patients with essential hypertension.

  Increased cardiorenal sympathetic nerves may be particularly noticeable in patients with heart failure. For example, excessive NE overflow from the heart and kidneys to plasma is often seen in these patients. Increased SNS activation usually characterizes both chronic kidney disease and end-stage renal disease. In patients with end-stage renal disease, NE plasma levels above average have been demonstrated to be predictive of cardiovascular disease and several causes of death. This is also true for patients suffering from diabetes or contrast nephropathy. Evidence suggests that sensory afferent signals originating from diseased kidneys are the primary cause of initiating and sustaining increased central sympathetic outflow.

Sympathetic nerves that innervate the kidney terminate in blood vessels, paraglomerular devices, and tubules. Renal sympathetic nerve stimulation can cause increased renin secretion, increased sodium (Na ⁺ ) reabsorption, and decreased renal blood flow. These neuromodulatory components of renal function are significantly stimulated in disease states characterized by increased sympathetic tone and can contribute to increased blood pressure in hypertensive patients. Reduction in renal blood flow and glomerular filtration rate as a result of efferent stimulation of the renal sympathetic nerve is the cornerstone of loss of renal function in cardiorenal syndrome (ie, renal dysfunction as a progressive complication of chronic heart failure) sell. Pharmacological strategies that prevent the consequences of efferent stimulation of the renal sympathetic nerve include centrally acting sympathetic blockers, beta blockers (intended to reduce renin secretion), angiotensin converting enzyme inhibitors and receptor antagonists. (Intended to block angiotensin II and aldosterone activation as a result of renin secretion), and diuretics (intended to antagonize sodium and water retention via renal sympathetic nerves). These pharmacological strategies, however, have significant limitations including limited effectiveness, compliance issues, side effects, and others. Therefore, there are strong public health requirements for alternative treatment strategies.

  Many aspects of the disclosure can be better understood with reference to the following drawings. The components in the figures are not necessarily drawn to scale. That is, an emphasis is placed on clearly illustrating the principles of the present disclosure.

1 illustrates a renal neuromodulation system configured in accordance with one embodiment of the present technology. FIG. FIG. 6 illustrates modulation of renal nerves with a catheter device according to an embodiment of the present technology. 2 is a graph depicting an energy delivery algorithm that may be used in conjunction with the system of FIG. 1 according to one embodiment of the present technology. FIG. 3 is a block diagram illustrating an algorithm for evaluating treatment according to an embodiment of the present technology. FIG. 3 is a block diagram illustrating an algorithm for evaluating treatment according to an embodiment of the present technology. FIG. 3 is a block diagram illustrating an algorithm for providing operator feedback upon occurrence of a high temperature condition according to an embodiment of the present technology. FIG. 3 is a block diagram illustrating an algorithm for providing operator feedback upon occurrence of a high impedance condition according to an embodiment of the present technology. 2 is a block diagram illustrating an algorithm for providing operator feedback upon the occurrence of a high degree of vasoconstriction according to one embodiment of the present technology. FIG. FIG. 3 is a block diagram illustrating an algorithm for providing operator feedback upon occurrence of an abnormal heart rate condition according to an embodiment of the present technology. FIG. 3 is a block diagram illustrating an algorithm for providing operator feedback when a low blood flow condition occurs according to an embodiment of the present technology. 2 is a screenshot illustrating an exemplary generator display screen configured in accordance with aspects of the present technology. 2 is a screenshot illustrating an exemplary generator display screen configured in accordance with aspects of the present technology. It is a conceptual diagram of a sympathetic nervous system (SNS), and is a figure which shows how a brain communicates with a body via SNS. FIG. 3 is an enlarged anatomical view of nerves that innervate the left kidney so as to form a renal plexus surrounding the left renal artery. 1 is an anatomical view of a human body depicting neurocentrifugal and afferent communication between the brain and kidney. 1 is a conceptual diagram depicting neurocentrifugal and afferent communication between brain and kidney. FIG. FIG. 3 is an anatomical diagram of human arterial vasculature. FIG. 3 is an anatomical diagram of human venous vasculature.

  The technology generally provides renal and neuronal modulation induced by electricity and / or heat (ie, deactivates or deactivates nerve fibers that innervate the kidney, or otherwise fully or partially functions. To devices, systems, and methods for providing useful assessment and feedback to clinicians or other professionals performing procedures such as In one embodiment, for example, the feedback relates to a completed treatment, in particular an assessment of the likelihood that the treatment was technically successful. In some embodiments, one or more parameters (such as parameters related to temperature, impedance, vasoconstriction, heart rate, blood flow, and / or patient movement) monitored during the course of treatment are defined. May be analyzed based on established criteria. Based on this analysis, an indication may be provided to the operator about the acceptability or lack of acceptability of the treatment based on the likelihood of technical success with the treatment.

  In other embodiments, due to a monitored value associated with temperature or impedance exceeding a predetermined and / or calculated threshold or a value determined to be outside the predetermined and / or calculated range. Feedback and / or instructions regarding the therapy that failed to complete, such as an abnormally terminated procedure, may be provided to the operator. In such embodiments, one or more parameters (such as parameters related to temperature, impedance, and / or patient movement) that are monitored during incomplete treatment are analyzed based on defined criteria. May be. Based on this analysis, whether the treatment site should be imaged to assess whether the treatment device may have been inadvertently moved, or additional treatment may be attempted. Additional instructions or feedback, such as whether or not, may be provided to the operator.

  Specific details of some embodiments of the technology are described below with reference to FIGS. Although many of the embodiments are described below with respect to devices, systems, and methods for evaluating neuromodulation therapy, other applications and other embodiments in addition to those described herein are also described in the present technology. Is within the range. Furthermore, some other embodiments of the present technology may have different configurations, components, or procedures than those described herein. Those skilled in the art may therefore have other embodiments with additional elements, or the techniques may be among the features shown and described below with reference to FIGS. It will be appreciated as appropriate that other embodiments without some may be present.

  The terms “distal” and “proximal” are used in the following description with respect to position or orientation relative to the treating clinician. “Distal” or “distal” is a position far from or away from the clinician. “Proximal” and “proximal” are positions close to or toward the clinician.

I. Renal nerve modulation Renal nerve modulation is a partial or complete loss of function or other effective disturbance of the nerves that innervate the kidney. In particular, renal neuromodulation includes inhibiting, reducing, and / or blocking neural communication along neural fibers that innervate the kidney (ie, efferent and / or afferent nerve fibers). Such loss of function can be long-term (eg, permanent or over a period of months, years, or decades), or short-term (eg, minutes, hours, days, or weeks). Over a period of time). Renal neuromodulation is associated with several clinical conditions characterized by increased total sympathetic activity, in particular hypertension, heart failure, acute myocardial infarction, metabolic syndrome, insulin resistance, diabetes, left ventricular hypertrophy, chronic kidney disease, It is expected to effectively treat conditions associated with central sympathetic hyperstimulation such as end-stage renal disease, inappropriate fluid retention in heart failure, cardiorenal syndrome, and sudden death. Decreased afferent nerve signals contribute to a systemic decrease in sympathetic tone / drive, and renal neuromodulation may be useful in treating several conditions associated with systemic sympathetic overactivity or enhancement There is expected. Renal neuromodulation can potentially serve various organs and body structures innervated by sympathetic nerves. For example, a decrease in central sympathetic drive may reduce insulin resistance that afflicts patients with metabolic syndrome and type II diabetes. In addition, osteoporosis can be activated by sympathetic nerves and can benefit from sympathetic drive down-regulation associated with renal neuromodulation. A more detailed description of the relevant patient anatomy and physiology is provided in Section IV below.

  Various techniques can be used to innervate the kidney but partially or completely lose function of neural pathways such as neural pathways. Intentional application of energy (eg, electrical energy, thermal energy) to tissue by the energy delivery element (s) is closely located or adjacent to the local area of the renal artery and the adventitia of the renal artery One or more desired thermal heating effects can be induced on adjacent regions of the renal plexus RP. Intentional application of the thermal heating effect can achieve neuromodulation along all or part of the renal plexus RP.

  Thermal heating effects can include both thermal ablation and non-ablative thermal alteration or damage (eg, via continuous heating and / or resistance heating). The desired thermal heating effect includes raising the temperature of the target neural fiber above a desired threshold that achieves non-ablative thermal alteration, or above a higher temperature that achieves ablative thermal alteration. But you can. For example, the target temperature may be above body temperature (eg, approximately 37 ° C.) for non-ablative thermal alteration but less than about 45 ° C., or the target temperature may be about 45 ° C. or higher for ablative thermal alteration. .

  More specifically, exposure to thermal energy (heat) above a body temperature of about 37 ° C. but below a temperature of about 45 ° C. is through moderate heating of the target neural fibers or the vascular structures that perfuse the target fibers. There is a possibility of inducing thermal alteration. If the vasculature is affected, the target nerve fibers are blocked from perfusion, resulting in necrosis of the neural tissue. For example, this can induce non-ablative thermal alteration in the fiber or structure. Exposure to heat above about 45 ° C. or above about 60 ° C. can induce thermal alteration through substantial heating of the fiber or structure. For example, such higher temperatures can thermally ablate target neural fibers or vascular structures. In some patients, thermally ablating the target neural fiber or vasculature but achieving a temperature that is less than about 90 ° C, or less than about 85 ° C, or less than about 80 ° C, and / or less than about 75 ° C May be desirable. Regardless of the type of thermal exposure used to induce thermal neuromodulation, a decrease in renal sympathetic nerve activity (“RSNA”) is expected. A more detailed description of the relevant patient anatomy and physiology is provided in Section IV below.

II. System and Method for Renal Nerve Modulation FIG. 1 illustrates a renal nerve modulation system 10 (“System 10”) configured in accordance with one embodiment of the present technology. System 10 includes an endovascular treatment device 12 operably coupled to an energy source or energy generator 26. In the embodiment shown in FIG. 1, the treatment device 12 (eg, a catheter) is distal to the proximal portion 18, a handle assembly 34 in the proximal region of the proximal portion 18, and the proximal portion 18. And an elongate shaft 16 having a distal portion 20 extending therethrough. The treatment device 12 further includes a treatment assembly or treatment area 22 that includes an energy delivery element 24 (eg, an electrode) at or near the distal portion 20 of the shaft 16. In the illustrated embodiment, the second energy delivery element 24 is broken to indicate that the systems and methods disclosed herein can be used with a treatment device having one or more energy delivery elements 24. Illustrated in. Furthermore, although only two energy delivery elements 24 are shown, it will be appreciated that the treatment device 12 may include additional energy delivery elements 24.

  The energy generator 26 (eg, RF energy generator) is configured to generate a selected form and size of energy for delivery to the target treatment site via the energy delivery element 24. The energy generator 26 can be electrically coupled to the treatment device 12 via a cable 28. At least one supply wire (not shown) communicates energy delivery element 24 along or through a lumen in elongated shaft 16 to transmit therapeutic energy to energy delivery element 24. A control mechanism, such as a foot pedal 32, is provided to enable the operator to initiate, terminate, and optionally adjust various operating features of the energy generator, including but not limited to power delivery. 26 (eg, pneumatically connected or electrically connected). The energy generator 26 can be configured to deliver therapeutic energy via an automatic control algorithm 30 and / or under the control of a clinician. Further, one or more evaluation / feedback algorithms 31 may be executed on the processor of the system 10. Such an evaluation / feedback algorithm 31 may provide feedback to the user of the system 10 when executed in conjunction with a therapy operation, for example, via the display 33 associated with the system 10. Feedback or evaluation may allow an operator of system 10 to determine the success of a given treatment and / or evaluate possible failure conditions. This feedback may therefore be useful to help the operator learn how to increase the likelihood of success when performing treatment. Further details regarding a suitable control algorithm 30 and evaluation / feedback algorithm 31 are described below with reference to FIGS. 3-10B.

  In some embodiments, the system 10 may be configured to provide delivery of a monopolar electric field via the energy delivery element 24. In such embodiments, a neutral or distributed electrode 38 may be electrically connected to the energy generator 26 and affixed to the outside of the patient (as shown in FIG. 2). In addition, one or more sensors (eg, thermocouples, thermistors, etc.), impedance sensors, pressure sensors, optical sensors, flow sensors, chemical sensors, or other sensors (not shown). May be in the vicinity of or within the energy delivery element 24 and connected to one or more of the supply wires (not shown). For example, a total of two supply wires may be included, where both wires can transmit signals from the sensor, one wire can serve a dual role, and energy is delivered to the energy delivery element. 24 could also be carried. Alternatively, both wires may be able to transmit energy to the energy delivery element 24.

  In embodiments including multiple energy delivery elements 24, the energy delivery element 24 may deliver power independently, either simultaneously, selectively, or sequentially (ie, used in a monopolar fashion). And / or power may be delivered between any desired combination of elements (ie, may be used in a bipolar fashion). In addition, the clinician optionally chooses which energy delivery element (s) for power delivery to form a highly customized lesion (s) in the renal artery as desired. It may be allowed to choose whether 24 is used.

  Computing devices in which system 10 is implemented include a central processing unit, memory, input devices (eg, keyboard and pointing device), output devices (eg, display devices), and storage devices (eg, disk drivers). But you can. The output device communicates with the treatment device 12 to control power to the energy delivery element 24 and / or to obtain a signal from the energy delivery element 24 or any associated sensor (eg, via cable 28). May be configured. The display device may be configured to provide an indicator of sensor data, such as power level or audio, visual, or other indicator, or may be configured to communicate information to another device. .

  Memory and storage are computer-readable media that may be encoded with computer-executable instructions that implement an object permission enforcement system, which means a computer-readable medium that contains instructions. Further, the instructions, data structures, and message structures may be stored or transmitted via a data transmission medium such as a signal on a communication link and may be encrypted. Various communication links may be used such as the Internet, a local area network, a wide area network, a point-to-point dial-up connection, a cellular phone network, and the like.

  Some embodiments of system 10 include personal computers, server computers, handheld or laptop devices, multiprocessor systems, microprocessor-based systems, programmable consumer electronics, digital cameras, network PCs, minicomputers, mainframes It may be implemented and used in conjunction with various operating environments including computers, computing environments including any of the systems or devices described above.

  System 10 may be described in the general context of computer-executable instructions, such as program modules, being executed by one or more computers or other devices. Generally, program modules include routines, programs, objects, components, data structures, etc. that perform particular tasks or implement particular abstract data types. Typically, the functionality of the program modules may be combined or distributed as desired in various embodiments.

  FIG. 2 (and with reference to FIG. 12) illustrates modulating the renal nerve in one embodiment of the system 10. The treatment device 12 passes through the intravascular pathway from the percutaneous access site in the femoral artery (illustrated), brachial artery, radial artery, or axillary artery to the target treatment site in the respective renal artery RA. Provide access to. As illustrated, the area of the proximal portion 18 of the shaft 16 is exposed outside the patient. By manipulating the proximal portion 18 of the shaft 16 from outside the intravascular pathway (eg, via the handle assembly 34), the clinician advances the shaft 16 through the often serpentine intravascular pathway and disengages the shaft. The positioning portion 20 may be remotely operated or started. Image guidance, such as computed tomography (CT), fluoroscopy, intravascular ultrasound (IVUS), optical coherence tomography (OCT), or another suitable guidance modality, or a combination thereof, may be provided to the clinician. It may be used to support the operation of Further, in some embodiments, image guidance components (eg, IVUS, OCT) may be incorporated within the treatment device 12 itself. Once proximity, alignment, and contact between the energy delivery element 24 and the tissue are established within each renal artery, the intentional application of energy from the energy generator 26 to the tissue by the energy delivery element 24 is One or more desired nerves on an adjacent region of the renal plexus RP that is closely located, adjacent to, or close to a local region of the renal artery and the adventitia of the renal artery Induces a modulation effect. Intentional application of energy may achieve neuromodulation along all or part of the renal plexus RP.

  The neuromodulation effect is generally at least partially a function of power, time, contact between the energy delivery element (s) 24 and the vessel wall, and blood flow through the vessel. Neuromodulating effects may include denervation, thermal ablation, and non-ablative thermal alteration or damage (eg, via continuous and / or resistance heating). The desired thermal heating effect includes raising the temperature of the target neural fiber above a desired threshold that achieves non-ablative thermal alteration, or above a higher temperature that achieves ablative thermal alteration. But you can. For example, the target temperature may be above body temperature (eg, approximately 37 ° C.) for non-ablative thermal alteration but less than about 45 ° C., or the target temperature may be about 45 ° C. or higher for ablative thermal alteration. . The desired non-thermal neuromodulation effect may include altering the electrical signal transmitted in the nerve.

III. Evaluation of renal neuromodulation therapy Overview In one implementation, a treatment administered using the system 10 delivers energy over a predetermined amount of time (eg, 120 seconds) through one or more energy delivery elements (eg, electrodes) to the inner wall of the renal artery. Configure to do. Multiple treatments (eg, 4-6) may be given in both the left and right renal arteries to achieve the desired coverage. The technical objective of the treatment may be, for example, to heat the tissue to a temperature that will damage the nerve to a depth of at least about 3 mm (eg, about 65 ° C.). The clinical purpose of the treatment typically neuromodulates (eg, damage) a sufficient number of renal nerves (either efferent or afferent nerves of the renal sympathetic plexus) to result in a reduction in sympathetic tone. To make it happen. If the therapeutic technical objective is achieved (eg, when the tissue is heated to about 65 ° C. to a depth of about 3 mm), the probability of a lesion in the renal nerve tissue being formed is high. As the number of technically successful treatments increases, the probability of modulating a sufficient percentage of renal nerves increases and therefore the probability of clinical success increases.

  Throughout the treatment, there may be a number of conditions that indicate the likelihood that the treatment will not be successful. In some embodiments, the operation of system 10 may be stopped or modified based on these status indicators. For example, certain indicators may result in a stoppage of energy delivery, and an appropriate message may be displayed on the display 33, for example. Factors that may result in display messages and / or treatment protocol cessation or correction include acceptable or expected out-of-threshold values and / or out-of-range impedance, blood flow, as determined or calculated And / or temperature measurements or indicators of change, but not limited to. The message may include the type of patient condition (eg, abnormal patient condition), the type and / or value of a parameter that is outside of acceptable or expected thresholds, an indication of action suggested to the clinician, or energy delivery It can show information like an indicator that is stopped. However, if unexpected or abnormal measurements are not observed, energy may continue to be delivered to the target site according to a programmed profile over a specified duration resulting in a completed treatment. After the treatment is complete, energy delivery may be stopped and a message indicating the completion of the treatment may be displayed.

  However, an event or combination of events may occur that alters (eg, reduces) the probability that a therapy is technically successful, even though the therapy can be completed without the onset of abnormal patient condition indications. For example, an electrode delivering energy may move or inadvertently be placed in inadequate contact between the electrode and the wall of the renal artery, resulting in inadequate lesion depth or temperature There is. Thus, it may be difficult to assess the technical success of a treatment, even when the treatment is complete without an indication of abnormal patient conditions. Similarly, to understand the cause of abnormal patient conditions (such as temperature and / or impedance values outside the expected range) as long as the system 10 may report an indication of abnormal patient conditions May be difficult.

  As described above, one or more evaluation / feedback algorithms 31 are provided that are executed on processor-based components of system 10, such as one or more components provided with generator 26. Also good. In such an implementation, one or more evaluation / feedback algorithms 31 can be used in evaluating a given treatment and / or the significance of certain types of abnormal patient conditions and the It may be possible to provide the user with meaningful feedback that can be used in learning how to reduce the occurrence. For example, if a particular parameter (eg, impedance or temperature value) indicates that the treatment did not proceed as expected or the treatment did not proceed as expected, in some cases as a result technically If there is a possibility of resulting in unsuccessful treatment, the system 10 can provide feedback (eg, via the display 33) to alert the clinician. The alert to the clinician is from simple notification of treatment failure to the treatment specific parameters during treatment (eg, impedance value (s), position of energy delivery element 24 within the patient, etc.) Can range up to the recommendation that it should be corrected. The system 10 can learn from the completed treatment cycle accordingly and modify subsequent treatment parameters based on such learning to improve effectiveness. Non-exhaustive examples of one or more evaluation / feedback algorithm 31 measurements include temperature change (s) over a specified time, maximum temperature, maximum average temperature, minimum temperature, predetermined or calculated Temperature at a given or calculated time for a given temperature, average temperature over a specified time, maximum blood flow, minimum blood flow, blood flow at a given or calculated time for a given or calculated blood flow, over time Average blood flow, maximum impedance, minimum impedance, impedance at a given or calculated time for a given or calculated impedance, impedance change over a specified time, or impedance to temperature change over a specified time It may be considered to include measurements related to changes in The measured value may be taken in one or more predetermined times, a time range, a calculated time, and / or a time when the measured event occurs or when it occurs. It will be appreciated that the above list merely provides a number of examples of different measurements, and other suitable measurements may be used.

B. Controlling applied energy With the treatments disclosed herein for delivering therapy to a target tissue, it may be beneficial for energy to be delivered to the target neural structure in a controlled manner. Controlled delivery of energy will allow the thermal treatment zone to extend into the renal fascia while reducing undesirable energy delivery or thermal effects to the vessel wall. Controlled delivery of energy can also result in a more consistent, predictable and efficient overall treatment. Accordingly, generator 26 desirably includes a processor that includes a memory component with instructions for executing algorithm 30 (see FIG. 1) for controlling power and energy delivery to the energy delivery device. The algorithm 30 whose exemplary embodiment is depicted in FIG. 3 may be implemented as a conventional computer program for execution by a processor coupled to the generator 26. Clinicians using step-by-step instructions may also implement algorithm 30 manually.

  The operating parameters monitored according to the algorithm may include, for example, temperature, time, impedance, power, blood flow, flow rate, volume flow, blood pressure, heart rate, and the like. Discontinuous values of temperature may be used to trigger changes in power or energy delivery. For example, high values of temperature (eg, 85 ° C.) can indicate tissue desiccation, in which case the algorithm reduces power and energy delivery to prevent undesirable thermal effects on target or non-target tissues. There is a possibility of causing or stopping. In addition or alternatively, time may be used to prevent unwanted thermal alteration to non-target tissue. For each treatment, a set time (eg, 2 minutes) is confirmed to prevent indefinite delivery of power.

  Impedance may be used to measure tissue changes. Impedance indicates the electrical characteristics of the treatment site. In a thermally inductive embodiment, when an electric field is applied to the treatment site, the impedance will decrease as the tissue cell becomes less resistant to current flow. If too much energy is applied, tissue desiccation or coagulation can occur near the electrode, which can cause cells to lose water retention and / or reduce electrode surface area (eg, via clot accumulation). ) Will increase the impedance. Thus, an increase in tissue impedance may indicate or be a precursor to undesirable thermal alteration to target or non-target tissue. In other embodiments, the impedance value may be used to assess contact between the energy delivery element (s) 24 and the tissue. For multiple electrode configurations (eg, when the energy delivery element (s) 24 include more than one electrode), where a relatively small difference between the impedance values of the individual electrodes indicates good contact with tissue There is. With a single electrode configuration, a stable value may indicate good contact. Thus, impedance information from one or more electrodes may be provided to a downstream monitor, which in turn provides an indication of the quality-related indication that the energy delivery element (s) 24 are in contact with the tissue. May be provided to a physician.

  In addition or alternatively, power is an effective parameter to monitor in controlling therapy delivery. Power is a function of voltage and current. The algorithm 30 may adjust the voltage and / or current to achieve the desired power.

  Derivatives of the above parameters (eg, rate of change) may also be used to trigger changes in power or energy delivery. For example, the rate of change of temperature may be monitored such that the power output is reduced in the event that a sudden temperature rise is detected. Similarly, the rate of change of impedance may be monitored such that the power output is reduced in the event that a sudden increase in impedance is detected.

As seen in FIG. 3, when the clinician initiates treatment (eg, via the foot pedal 32 illustrated in FIG. 1), the control algorithm 30 sets its power output to the first time period t ₁ ( For example, to the generator 26 that gradually adjusts to a _first power level P ₁ (eg, 5 Watts) over 15 seconds). The power increase during the first time period is generally linear. As a result, generator 26 increases its power output at a generally constant rate of P ₁ / t ₁ . Alternatively, the power increase may be non-linear (eg, exponential or parabolic) with a variable rate of increase. Once P ₁ and t ₁ are achieved, the algorithm may be held at P ₁ for a predetermined time period t ₂ -t ₁ (eg, 3 seconds) until a new time t ₂ . At t ₂ , power is increased to P ₂ by a predetermined increment (eg, 1 watt) over a predetermined time period t ₃ -t ₂ (eg, 1 second). This power ramp-up in a predetermined increment of about 1 watt over a predetermined time period may continue until the maximum power P _MAX is achieved or some other condition is met. In one embodiment, P _MAX is 8 watts. In another embodiment, P _MAX is 10 watts. Optionally, the power may be maintained at a maximum power P _MAX for a desired time period or up to a desired total treatment time (eg, up to about 120 seconds).

  In FIG. 3, algorithm 30 illustratively includes a power control algorithm. However, it should be understood that the algorithm 30 may alternatively include a temperature control algorithm. For example, the power may be gradually increased until a desired temperature (or several temperatures) is obtained over a desired duration (or several durations). In another embodiment, a combined power control and temperature control algorithm may be provided.

  As stated, the algorithm 30 includes monitoring certain operating parameters (eg, temperature, time, impedance, power, flow rate, volume flow, blood pressure, heart rate, etc.). The operating parameters may be monitored continuously or periodically. The algorithm 30 checks the monitored parameter against the predetermined parameter profile to determine whether the parameters are individually or combined and fall within the range set by the predetermined parameter profile. If the monitored parameter falls within the range set by the predetermined parameter profile, treatment may continue at the commanded power output. If the monitored parameter is outside the range set by the predetermined parameter profile, the algorithm 30 adjusts the commanded power output accordingly. For example, if a target temperature (eg, 65 ° C.) is achieved, power delivery will remain constant until the entire treatment time (eg, 120 seconds) has elapsed. If the first temperature threshold (eg, 70 ° C.) is achieved or exceeded, the power is reduced in predetermined increments (eg, 0.5 watts, 1.0 watts, etc.) until the target temperature is achieved. . If a second power threshold (eg, 85 ° C.) is achieved or exceeded, indicating an undesirable condition, power delivery may be terminated. The system may include various audible and visual alerts to alert an operator of certain conditions.

  The following is a non-exhaustive list of events that the algorithm 30 may adjust and / or terminate / stop the commanded power output below.

  (1) The measured temperature exceeds a maximum temperature threshold (eg, from about 70 to about 85 ° C.).

  (2) The average temperature derived from the measured temperature exceeds an average temperature threshold (eg, about 65 ° C.).

  (3) The rate of change of the measured temperature exceeds the rate of change threshold.

  (4) The temperature rise over a period of time with the generator 26 having a non-zero output falls below the minimum temperature change threshold. Poor contact between the energy delivery element (s) 24 and the arterial wall can cause these conditions.

  (5) The impedance being measured exceeds or is outside the impedance threshold (eg, <20 ohms or> 500 ohms).

  (6) The measured impedance exceeds a relative threshold (eg, the impedance decreases from a starting value or baseline value and then rises above this baseline value)

  (7) The measured power exceeds the power threshold (eg,> 8 watts or> 10 watts).

  (8) The measured power delivery duration exceeds the time threshold (eg,> 120 seconds).

  Advantageously, the magnitude of the maximum power delivered during renal neuromodulation therapy according to the present technology is, for example, cardiac tissue ablation (eg, a power level greater than about 15 watts, greater than about 30 watts, etc.). May be relatively low compared to the power level used in electrophysiological therapy to achieve (eg, less than about 15 watts, less than about 10 watts, less than about 8 watts, etc.). Since relatively low power levels may be used to achieve such renal neuromodulation therapy, the energy delivery element and / or non-target tissue may be brought to or below a desired temperature (eg, about 50 ° C.) during power delivery. The intravascular infusion flow rate and / or total volume required to maintain at or below, eg, at or below about 45 ° C. is also higher than that used, for example, in electrophysiological therapy It may be relatively lower than may be required at power levels (eg, power levels above about 15 watts). In some embodiments where forced cooling is used, the relative reduction in intravascular infusate infusion flow rate and / or total volume advantageously has a higher power level, and therefore a correspondingly higher infusate rate. Can facilitate the use of intravascular infusions in higher risk patient groups (eg, patients with heart disease, heart failure, renal dysfunction and / or diabetes mellitus) where the use of / volume would have been contraindicated There is sex.

C. Technical Evaluation of Treatment FIG. 4 is a block diagram of a treatment algorithm 80 configured in accordance with one embodiment of the present technology. The algorithm 80 is configured to evaluate events in the treatment, determine the technical success probability of the treatment, and display appropriate messages to provide feedback to the operator of the system 10 (or another suitable treatment system). The If it is determined that the treatment has a predetermined technical success probability that is not sub-optimal, a message may be displayed indicating that the treatment did not proceed as expected. Alternative implementations can classify treatments into several ranges of success probabilities, such as success probabilities on the scale of 1-5. Similarly, in some implementations, the algorithm 80 can evaluate whether the treatment belongs to a high success probability category, a very low probability of success category, or somewhere in between.

  Variables that characterize the treatment and that may be used by the algorithm 80 in evaluating the treatment are time (ie, duration of treatment), power, temperature change, maximum temperature, average temperature, blood flow, temperature, or impedance. Including but not limited to standard deviation, impedance change, or a combination of these or other variables. For example, some or all variables may be provided to the algorithm 80 as treatment data 82. In this generalized depiction of algorithm 80, treatment data 80 may be evaluated based on a cascade or series of different categories or degrees of criteria 84. A favorable evaluation of treatment data 82 in light of one of criteria 84 may result in the display of a message indicating that the treatment was acceptable or successful (block 86). If treatment data 82 is not found acceptable against criteria 84, the treatment data may eventually be lowered to the next assessment criteria 84.

  In the illustrated embodiment, additional treatments such as the illustrated analysis and scoring step 88 are performed if the treatment data is not found acceptable against all criteria 84. Also good. The output of the analysis and scoring step (eg, score 90) may be evaluated (block 92). Based on this assessment 92, the treatment is deemed acceptable and a corresponding screen is displayed (block 86) or considered unacceptable and a screen 94 indicating that the treatment did not proceed as expected. May be displayed. In a further embodiment, the algorithm 80 may include an automatic action (eg, an automatic decrease in the power level supplied to the energy source) in response to an indication that the therapy did not proceed as expected.

  While FIG. 4 depicts a generalized and simplified implementation of a treatment evaluation algorithm, FIG. 5 depicts a more detailed example of one embodiment of the treatment evaluation algorithm 100. The treatment evaluation algorithm 100 may be calculated after completion of the treatment (block 102), which may be 120 seconds long (as shown) or some other suitable duration, Data and / or measurements derived during the course of treatment may be used.

  In the illustrated embodiment, when the electrodes are not in consistent contact with the vessel wall, it is likely that sub-ideal treatment will most likely occur. Accordingly, the decision blocks 104, 106, 108, and 110 of the flowchart are associated with different criteria and are outside of a predetermined range (i.e., a high success probability based on data 102 observed or measured in the course of treatment completion. Screen treatments that appear to have one or more criteria (not). In the illustrated embodiment, treatments that are not screened at decision blocks 104, 106, 108, and 110 enter a linear discriminant analysis (LDA) 112 to further evaluate the treatment. In other embodiments, other suitable analyzes may be performed instead of the illustrated LDA. The value assigned to each step (ie assessment according to the respective criteria) and the coefficient 114 used in the LDA can be derived from data collected from several treatments and / or experience obtained from animal experiments. .

  In the illustrated embodiment, the first decision block 104 evaluates the initial temperature response to energy delivery by ascertaining whether the average temperature change in the first 15 seconds is greater than 14 ° C. . In one implementation, average temperature refers to an average over a short amount of time (eg, 3 seconds), which inherently filters out large and frequent fluctuations caused by pulsatile blood flow. As is probably understood, the temperature increase of the treatment electrode is the result of heat transfer from the tissue to the electrode. If the electrode is not in full contact with the vessel wall, energy is delivered into the blood flowing around it and the temperature of the electrode does not increase that much. With this in mind, if the change in average temperature in the first 15 seconds is greater than, for example, 14 ° C., this initial temperature response is at least sufficient electrode contact, contact force, and / or blood at the start of treatment. There is no high probability that the treatment was suboptimal or technically unsuccessful if it does not face the indication that the treatment did not proceed as expected over the remainder of the treatment, which may indicate flow. Accordingly, an affirmative response at decision block 104 results in a “treatment complete” message 120 being displayed. However, if the average temperature change in the first 15 seconds is, for example, less than or equal to 14 ° C., this initial temperature response may indicate that the electrode did not have sufficient contact with the vessel wall. May indicate. Accordingly, a negative response at decision block 104 results in advancing to criteria 106 for further evaluation.

  At decision block 106, the hottest temperature is evaluated by ascertaining whether the maximum average temperature is greater than, for example, 56 ° C. A temperature increase above a threshold level (eg, 56 ° C.) may be sufficient to allow technical success regardless of duration. Thus, the temperature above the threshold may be sufficient to indicate successful lesion formation despite the fact that the initial temperature rise at decision block 104 did not indicate sufficient contact. For example, the electrode may not have had sufficient contact initially, but then contact has been made for at least sufficient time to heat the vessel wall such that the temperature sensor reading in the electrode is above 56 ° C. It may have been made. A positive result at decision block 106 results in a “treatment complete” message 120 being displayed. However, a negative result at decision block 106 indicates that the maximum average temperature did not rise sufficiently. The algorithm 100 therefore proceeds to decision block 108 for further evaluation.

  At decision block 108, the average temperature is evaluated during the period when power is sustained at that maximum amount (ie, the startup period is excluded from the average calculation). In one embodiment, this evaluation consists of determining whether the average real-time temperature is above 53 ° C. during a period of 45 seconds to 120 seconds. Thus, this criterion confirms the determination of whether the temperature has exceeded a threshold for a certain duration. If decision block 108 yields a positive determination, the fact that the initial temperature response and the highest average temperature were insufficient to indicate technical success (ie, failed decision blocks 104 and 106) Nevertheless, the average temperature for the last 75 seconds indicates sufficient contact for a sufficient time. For example, the maximum average temperature measured at the electrode may not have exceeded 56 ° C. because sufficient damage has been created, but there is a high blood flow that draws heat from the electrode. Accordingly, a positive result at decision block 108 causes a “treatment complete” message 120 to be displayed. However, a negative result at decision block 108 indicates that the average real-time temperature at the sustained power stage was not sufficient and the algorithm 100 proceeds to decision block 110 for further evaluation of treatment.

決定ブロック１１０が肯定的判定をもたらす場合、前の３つの決定ブロックが十分な温度上昇があったことを示さなかった（すなわち、決定ブロック１０４、１０６、及び１０８で不合格であった）という事実にもかかわらず、インピーダンスの変化は、組織が十分に加熱されたが電極の中の温度センサが十分に上昇しなかったことを示すことができる可能性がある。例えば、非常に高い血流は、組織が加熱された場合であっても電極温度を比較的低いままにする可能性がある。したがって、決定ブロック１１０での肯定的結果により、結果的に「治療完了」メッセージ１２０が表示される。しかしながら、決定ブロック１１０での否定的結果により、結果的にアルゴリズム１００がＬＤＡ１１２を行うことに進む。 At decision block 110, the impedance is determined by checking whether the rate of change in impedance during a predetermined period (eg, 45 seconds to 114 seconds) is greater than a predetermined value (eg, 14%) of the initial impedance. Changes are evaluated. The initial impedance is determined as the impedance immediately after the start of treatment (eg, at 6 seconds) to eliminate possible misreading (eg, due to contrast agent injection) in impedance measurements prior to this period. As is probably understood, the tissue impedance to radio frequency (RF) current decreases with increasing tissue temperature until the tissue is sufficiently heated and dry, and when the tissue is fully heated and dried. Its impedance begins to rise. Thus, a decrease in tissue impedance can indicate an increase in tissue temperature. The rate of change of real-time impedance over a sustained power stage may be calculated as follows:

If decision block 110 provides a positive determination, the fact that the previous three decision blocks did not indicate that there was a sufficient temperature rise (ie, failed decision blocks 104, 106, and 108) Nevertheless, a change in impedance may be able to indicate that the tissue has been heated sufficiently but the temperature sensor in the electrode has not risen sufficiently. For example, very high blood flow can leave the electrode temperature relatively low even when the tissue is heated. Thus, a positive result at decision block 110 results in a “treatment complete” message 120 being displayed. However, a negative result at decision block 110 results in algorithm 100 proceeding to perform LDA 112.

  At LDA 112, the combination of events is evaluated along with an importance rating for each event. In the illustrated embodiment, for example, criteria evaluated at decision blocks 104, 106, 108, 110 are included in LDA 112. In addition, this implementation provides three additional criteria: (1) standard deviation of mean temperature (can provide an indication of the degree of sliding movement caused by breathing), (2) real-time temperature Standard deviation (which can provide an indication of changing blood flow and / or contact force and / or intermittent contact), and (3) a controlled change in average impedance at the end of treatment Characterization, which can provide an indication of tissue temperature change). If this analysis determines that the combination of variables has a significant impact on reducing technical success (eg, LDA score <0 at decision block 122), an “expected treatment” message 124 is displayed. In another method, a “treatment complete” message 120 is displayed.

  The various parameters described above are merely representative examples associated with one embodiment of algorithm 100, and one or more of these parameters may vary in other embodiments. Will be understood. Furthermore, the specific values described above for a particular portion of therapy may be modified / changed in other embodiments based on, for example, different device configurations, electrode configurations, therapy protocols, and the like.

  As described above, the algorithm 100 is configured to evaluate the treatment and display a message indicating that the treatment is complete, or alternatively that the treatment did not proceed as expected. Based on the message describing the assessment of the treatment, the clinician (or system using automated technology) can then determine whether further treatment may be required and / or one or more parameters modified in subsequent treatments. It can be decided whether or not to be done. In the example described above, for example, the algorithm 100 evaluates a number of situations that are generally associated with poor contact between the electrode and the vessel wall to help determine when treatment is not optimal. May be. For example, when the electrode is slid back and forth when the patient is breathing and the artery is moving, when the electrode is displaced when the patient is moved, the catheter is inadvertently moved and when the catheter is inadvertently moved, Poor contact can occur when not being deflected to the extent necessary to apply sufficient contact or contact force between and / or when the electrode is placed in an uncertain position. Further, as explained above, if a particular parameter or set of parameters may have contributed to or resulted in a suboptimal treatment, the system 10 (FIG. 1) may then Feedback may be provided to alert the clinician to modify one or more treatment parameters during treatment. These assessments and feedback of treatment are expected to help clinicians learn to improve their positioning techniques to obtain better contact and reduce the frequency of technically unsuccessful treatments.

D. Feedback related to high temperature conditions While the above describes a generalized assessment of the technical success of a therapy, another form of feedback that may be useful to the operator of the system 10 (FIG. 1) is Feedback related to the type of patient or treatment condition. For example, the system 10 may generate a message related to a high temperature condition. In particular, tissue temperature can increase above a specified level while energy is delivered during treatment. A temperature sensor (eg, thermocouple, thermistor, etc.) positioned in or near the electrode provides an indication of the temperature of the electrode, and in part, an indication of tissue temperature. The electrode is not heated directly as energy is delivered to the tissue. Instead, the tissue is heated and heat is conducted to the electrode and the temperature sensor in the electrode. In one implementation, the system 10 may cease energy delivery when the real time temperature rises above a predetermined maximum temperature (eg, 85 ° C.). In such an event, the system may generate a message indicating a high temperature condition. However, depending on the situation, different actions by the clinician may be appropriate.

  If the tissue becomes too hot, an established temperature threshold may be exceeded. The effect of high tissue temperature is that acute contraction of the artery or protrusion of the arterial wall can occur. This may occur immediately or within a short period of time after the occurrence of a high temperature is observed and a message is generated (eg, it may occur from about 50 seconds to about 100 seconds). In such an event, the clinician may be instructed to image the treatment site to watch for contractions or protrusions before initiating another treatment.

  FIG. 6 is a block diagram illustrating an algorithm 150 for providing operator feedback, for example, when a high temperature condition is detected according to one embodiment of the present technology. In one implementation, the algorithm 150 is executed in response to a high temperature condition (block 152) and uses data from the treatment to determine if the high temperature condition involved or did not involve a situation involving sudden instability. Evaluate (decision block 154). Sudden instability can be caused, for example, by sudden movement of the patient or catheter and the electrode being pushed strongly into the vessel wall (ie, increasing contact force) May involve travel to location. In an event where a sudden instability is not detected at decision block 154, a first message such as an indication that a high temperature has been detected and an instruction to image the treatment site to determine whether the site is damaged May be displayed (block 156). In the event that sudden instability is detected at decision block 154, in addition to indicating the occurrence of a high temperature and instructing the clinician to image the treatment site, the electrode may have been moved from its original site An alternative message may be displayed that may indicate that there is (block 158). Such feedback may prompt the clinician to compare with the previous image and avoid retreating either at the original site or at the site where the electrode has been moved.

E. Feedback Related to High Impedance Similar to high temperatures, in some situations, system 10 (FIG. 1) may generate a message related to the occurrence of high impedance. As will be appreciated, the impedance from the treatment electrode to the RF current flowing through the body to the distributed return electrode can provide an indication of the characteristics of the tissue in contact with the treatment electrode. For example, an electrode positioned in the blood flow in the renal artery may measure a lower impedance than an electrode that contacts the vessel wall. Furthermore, as the tissue temperature increases, its impedance decreases. However, if the tissue gets too hot, it can dry out and its impedance can increase. It is expected that the impedance will decrease as the tissue is gradually heated during treatment. A significant increase in impedance can be the result of undesirable conditions such as tissue drying or electrode movement. In some implementations, the system 10 may be configured to stop energy delivery when the increase in real-time impedance exceeds a predetermined maximum change in impedance from the starting impedance.

  FIG. 7 is a block diagram illustrating an algorithm 170 for providing operator feedback upon occurrence of a high impedance condition, for example, according to one embodiment of the present technology. In the illustrated embodiment, the algorithm 170 evaluates the data from the treatment and the detection of the high impedance event (block 172) is: (a) a situation where the tissue temperature is high and desiccation may have occurred ( Determine whether it may have been involved in a situation where b) the electrode was moved, or (c) a poor or no electrode contact with the vessel wall. The algorithm 170 evaluates the data to determine which of these three situations, if any, and displays one of the three messages 174, 176, or 178 as appropriate.

  According to one embodiment of algorithm 170, upon detecting a high impedance (block 172), the highest average temperature during treatment is evaluated (decision block 180). If this temperature is above a certain threshold (eg, 60 ° C. or higher), the high impedance may be due to the high tissue temperature that results in desiccation. At this event, a message 174 may be displayed instructing the clinician to confirm the contraction or protrusion (ie, to image the treatment site) and avoid treating again at the same location. . Conversely, if the temperature is below a threshold (eg, below 60 ° C.), the algorithm 170 proceeds to decision block 182.

  In the illustrated embodiment, at decision block 182, the algorithm 170 evaluates whether a high impedance event occurred early in therapy (eg, during the first 20 seconds of energy delivery) when power is relatively low. To do. If yes, the tissue temperature is unlikely to be high and the electrode has a poor contact or no contact first, and then a better contact is more likely established that causes the impedance to jump . In this event, a message 176 may be displayed instructing the clinician to attempt to establish better contact and repeat the treatment at the same site. However, if the event occurs later in the treatment (eg, after 20 seconds or more), the algorithm 170 proceeds to decision block 184.

  At decision block 184, the algorithm 170 evaluates when a high impedance event has occurred during treatment. For example, if an event occurs after a predetermined time period (eg, 45 seconds), the algorithm proceeds to decision block 186 when the power reaches a high level. However, if the event occurs when power is rising and not at its maximum (eg, between 20 and 45 seconds), the algorithm proceeds to decision block 188.

％ΔＺが所定の量（例えば、７％）よりも大きい又はこれに等しい場合、高温に起因して組織が乾燥し始めた可能性が高い。このイベントでは、臨床医に収縮又は突出を確認するように（すなわち、治療部位を画像化するように）及び同じ場所で再び治療することを回避するように指示するメッセージ１７４が表示されてもよい。他の場合には、組織乾燥が起こる可能性が低く、電極が動かされて高インピーダンス・イベントが引き起こされる可能性がより高い。このイベントでは、電極が動かされた可能性があることを臨床医に通知するメッセージ１７８が表示されてもよい。電極が動かされた又は動かされた可能性があるイベントでは、組織温度が高いレベルに達することはまずない。したがって、同じ場所での治療は、別の治療を行うための他の場所がない又は限られた他の場所がある場合に行われることがあることが予期される。 At decision block 186, the algorithm 170 calculates the rate of change in impedance (% ΔZ) during a high impedance event compared to the impedance at a specified time (eg, 45 seconds). This is the period when power is sustained at a high level. In one embodiment, the rate of change of impedance is calculated as follows:

If% ΔZ is greater than or equal to a predetermined amount (eg, 7%), it is likely that the tissue has started to dry due to high temperatures. At this event, a message 174 may be displayed instructing the clinician to confirm the contraction or protrusion (ie, to image the treatment site) and avoid treating again at the same location. . In other cases, tissue desiccation is unlikely to occur and the electrode is more likely to cause a high impedance event. In this event, a message 178 may be displayed notifying the clinician that the electrode may have been moved. In events where the electrode has been moved or may have been moved, the tissue temperature is unlikely to reach a high level. Thus, it is expected that treatment at the same location may be performed when there are no other places to perform another treatment or there are limited other places.

  At decision block 188, the algorithm 170 may determine whether a sudden instability has occurred. If this instability exists, it is likely that the electrode has been moved. In this event, a message 178 may be displayed notifying the clinician that the electrode may have been moved. As noted above, the clinician may be careful to avoid treating the original location or the location where the electrode was moved, or the clinician may have other sites available for further treatment. If no or a limited number of sites are available, one may choose to treat at the same location. Otherwise, if no sudden instability occurred, it is more likely that the electrode had poor contact. In this event, a message 176 may be displayed instructing the clinician to attempt to establish better contact and indicating that treatment at the same site is safe.

  The same purpose of detecting high impedance conditions can be achieved using alternative measurements and calculations. For example, in a further embodiment of algorithm 170, temperature and impedance data are taken every sample time interval (eg, 20 seconds). At shorter time intervals (eg every 1.5 seconds), standard deviations of impedance and temperature data are calculated. The first standard temperature for a time interval is calculated as the temperature standard deviation divided by the temperature standard deviation in the first time interval. If the standard deviation of the impedance measurement is greater than or equal to a predetermined value (eg, 10 ohms) and the first standard temperature is greater than a predetermined threshold value (eg, 3), then the algorithm 170 may cause poor electrode contact. A message 176 indicating can be displayed. However, if the standard deviation of the impedance measurement is outside the acceptable range, but the first standard temperature is within the acceptable range, message 178 to alert the clinician that electrode instability exists. Will be displayed.

  According to a further embodiment of algorithm 170, the impedance of two or more electrodes 24 (eg, positioned on treatment region 22 of catheter 12 of FIG. 1) can each provide an independent impedance reading. . During delivery of the treatment assembly 22 to the treatment site (eg, within the renal artery), the catheter 12 conforms to the minimum resistance path and often bends at the curvature of the vasculature and contacts only one wall of the renal artery. As such, the impedance reading of the electrode 24 typically varies due to the anatomy of the vasculature. In some embodiments, once the treatment assembly 22 is in a position for treatment, the treatment assembly 22 can be expanded circumferentially to contact the entire circumferential surface of a segment of the renal artery wall. This expansion can leave a plurality of electrodes 24 in contact with the renal artery wall. As the treatment assembly 22 is expanded to the treatment configuration and the contact between the electrode 24 and the renal artery wall increases, the impedance value of the individual electrode 24 can increase and / or approach the same value. In good and stable contact conditions, the variation in impedance value is also reduced as explained above. The energy generator 26 can continuously or continuously monitor individual impedance values. The values can then be compared to determine when contact has been made effectively as an indicator of successful treatment. In a further embodiment, the moving average of the impedance can be compared to a predetermined range of variability in impedance values with limits set to guide the stabilizing means.

F. Feedback Related to Vasoconstriction In a further embodiment, system 10 may generate a message related to the occurrence of vasoconstriction. In particular, blood vessels can contract to suboptimal diameters during treatment delivery. Contracted blood vessels can lead to decreased blood flow, increased treatment site temperature, and increased blood pressure. Vasoconstriction can be measured by sampling the amplitude (“envelope”) of real-time temperature data. The current envelope can be compared to the previous envelope sample taken (eg, 200 ms before). The difference between the current envelope and the previous time point envelope is less than a predetermined value (eg less than −0.5 ° C., in other words, the current envelope relative to the envelope value at the previous time point). If there is a decrease of less than 0.5 degrees in the value), the measurement is taken at a future time point (eg at 5 seconds). If the difference between the average temperature at the future time point and the current time point is greater than a given temperature threshold (eg, greater than 1 ° C.), the algorithm 800 indicates that an undesirably high level of contraction exists. Can be determined and energy delivery can be stopped / changed. In such an event, the system 10 may generate a message indicating a high contraction condition. However, depending on the situation, different actions by the clinician may be appropriate.

  FIG. 8 is a block diagram illustrating an algorithm 800 for providing operator feedback when, for example, a high degree of vasoconstriction is detected according to one embodiment of the present technology. In one implementation, the algorithm 800 is performed in response to a high contraction level (eg, a blood vessel that contracts to or below a certain diameter) (block 802), and the high contraction level includes a sudden instability. Data from the treatment is evaluated to determine if it was involved or not (decision block 804). An indication of sudden instability can indicate that the electrode 24 has moved.

  In an event where sudden instability is not detected at decision block 804, a first message may be displayed, such as an indication that a high contraction level has been detected and an instruction to the clinician to reduce treatment power. (Block 806). In further embodiments, the energy level may be automatically changed in response to the detected contraction level. In the event that sudden instability is detected at decision block 804, in addition to indicating the occurrence of a high contraction level and instructing the clinician, it may indicate that the electrode 24 may have been moved from its original site. An alternative message may be displayed (block 808). Such feedback may prompt the clinician to change or stop treatment.

G. Feedback related to cardiac factors Feedback Related to Abnormal Heart Rate Similar to the other physiological conditions described above, in some situations, system 10 may generate a message related to the occurrence of an abnormal heart rate. In particular, while the therapy is being delivered, the heart rate may exceed or fall below a desired condition (eg, temporary therapeutic or chronic bradycardia). Instantaneous heartbeats can be determined by measuring real time temperature and impedance. More specifically, the real-time temperature reading can be filtered, for example between 0.5 Hz and 2.5 Hz, using a second order Butterworth filter. The maximum of the filtered signal is determined. The maximum is the detected peak of the true temperature signal. Since the signal peak corresponds to a periodic change in the cardiac cycle, the instantaneous heartbeat is the interval between the peaks.

  In one implementation, the system 10 may stop / change energy delivery when the heart rate is outside the desired range. In such an event, the system may generate a message indicating an unfavorable heartbeat condition. However, depending on the situation, different actions by the clinician may be appropriate.

  FIG. 9A is a block diagram illustrating an algorithm 900 for providing operator feedback / instructions upon detection of an abnormal heart rate condition, for example, according to one embodiment of the present technology. In one implementation, for example, the algorithm 900 may be performed in response to an abnormal heart rate condition (eg, above or below a predetermined threshold) (block 902). At decision block 904, the algorithm 900 evaluates the data from the treatment to determine whether the detected abnormal heart rate condition involved a situation involving sudden instability. A sudden instability indicator can indicate that the electrode has been moved.

  For events where no sudden instability is detected at decision block 904, a first message is displayed to the clinician, such as an indication that an abnormal heartbeat has been detected and an instruction to the clinician to reduce treatment power. (Block 906). In a further embodiment, the energy level may be changed automatically in response to a detected adverse heartbeat. In the event that sudden instability is detected at decision block 904, in addition to indicating the occurrence of an abnormal heartbeat and instructing the clinician, the electrode may have been moved from its original site An alternative message may be displayed (block 908). Such feedback may prompt the clinician to change or stop treatment.

2. Feedback system 10 related to low blood flow may also be configured to generate messages related to low blood flow conditions. For example, if blood flow is reduced below a certain level during treatment (or if blood vessels are undesirably narrow), the convective heat removed from the electrode 24 and the tissue surface is reduced. An excessively high tissue temperature can lead to the negative outcomes described above, such as thrombosis, charring, unreliable lesion size, and the like. Reducing the power from the generator 26 to prevent the tissue from reaching an unacceptable temperature may lead to insufficient lesion depth and the nerve may not be heated to a sufficient ablation temperature. An algorithm can be used to measure the loss of heat to the bloodstream or blood flow. In one embodiment, blood flow can be measured with a flow meter or Doppler sensor placed in the renal artery, on a separate catheter, or on the treatment catheter 12. In another embodiment, heat loss or thermal decay can be measured by delivering energy (eg, RF energy) to increase blood, tissue, or substrate temperature. The energy can be turned off and the algorithm can include monitoring temperature as a measure of thermal decay. Rapid thermal decay can represent sufficient blood flow, while slow thermal decay can represent low blood flow. For example, in one embodiment, if the slope of the real-time temperature measurement above the starting temperature exceeds a preset threshold (eg, 2.75) and the average temperature is higher than the preset temperature (eg, 65 ° C.), an algorithm 910 can indicate low blood flow. In a further embodiment, thermal attenuation and / or blood flow can be characterized by measuring temperature fluctuations of electrodes that deliver RF or resistive heat. For a given temperature or power delivery amplitude / magnitude, a narrow range of variation can indicate a relatively low thermal attenuation / blood flow.

  FIG. 9B is a block diagram illustrating an algorithm 910 for providing operator feedback / instructions upon occurrence of a low blood flow condition, for example, according to one embodiment of the present technology. In one implementation, the algorithm 910 is executed in response to a detected low blood flow condition (eg, flow below a predetermined threshold) (block 912). At block 914, the algorithm 910 evaluates the data from the treatment to determine if the low blood flow condition was involved in a situation involving sudden instability. In an event where sudden instability is not detected at decision block 914, a first message may be displayed, such as an indication that low blood flow is being detected and an instruction to the clinician to reduce treatment power. (Block 916). In the event that sudden instability is detected, in addition to indicating the occurrence of low blood flow and instructing the clinician, an alternative message that may indicate that the electrode may have been moved from its original site May be displayed (block 918). As noted above, such feedback may prompt the clinician to change or stop treatment.

  In a further embodiment, if the blood flow or thermal attenuation value is below a typical or predetermined threshold, the energy delivery algorithm 910 may determine one or more conditions of the treatment or catheter to improve blood flow or It can include changing features automatically. For example, in one embodiment, algorithm 910 can accommodate low blood flow by pulsing the energy provided to energy delivery element 24 rather than providing continuous energy. This may allow lower blood flow to better remove heat from the tissue surface while still resulting in a lesion that is deep enough to ablate the nerve.

  In another embodiment, the algorithm 910 is based on International Patent Application No. PCT / US2011 / 033491 filed on April 26, 2011 and US Patent Application No. 12 / 874,457 filed on August 30, 2010. Addressing low blood flow by cooling the electrodes as described in more detail in the section. The above applications are incorporated herein by reference in their entirety.

  In a further embodiment, the algorithm 910 can accommodate low blood flow by requiring a manual increase in blood flow to the region. For example, a non-occlusive balloon can be inflated in the abdominal aorta to increase pressure and flow in the renal arteries. The balloon can be incorporated on the treatment catheter or a separate catheter.

H. Feedback Display FIGS. 10A and 10B are screenshots illustrating a typical generator display screen configured in accordance with aspects of the present technology. FIG. 10A is a display screen 1100 for enhanced impedance tracking, eg, during treatment. Display 1100 includes a graphical display 1110 that tracks impedance measurements in real time over a selected time period (eg, 100 seconds). This graphical display 1110 can be, for example, a dynamic rolling display that is updated at regular intervals to provide the operator with both instantaneous and historical tracking of impedance measurements. The display 1110 can also include an impedance display 1120 with a standard deviation indicator 1122 regarding the current impedance as well as the impedance. In one embodiment, the standard deviation indicator 1122 is configured to flash when this value is greater than 10. Such an indicator can alert the operator that contrast agent injection is affecting the measurement or that the electrode may be unstable. Further information regarding contrast agent injection indices is described below.

  FIG. 10B is another exemplary display screen 1130 with additional information for an operator, for example. In this example, the display screen 1130 is configured to alert the operator of contrast agent injection, and the system waits for the contrast agent to clear before starting (eg, approximately 1 until the contrast agent is cleared). Disable RF for ~ 2 seconds). In another embodiment, display screen 1130 may be configured to provide other warning messages (eg, “electrode may be unstable”, etc.). The additional information provided on the display screens 1110 and 1130 described above is expected to improve contact assessment before turning on RF and improve the efficiency and effectiveness of treatment.

  The additional information described above with reference to FIGS. 10A and 10B can be generated based on the algorithms described herein or other suitable algorithms. In one embodiment, for example, the algorithm can continuously check contrast agent injection / stability until RF is turned on. If the electrode is stable and no contrast agent is present for ≧ 1 second, the baseline impedance Z is set equal to the average impedance Z over 1 second. In one particular example, the real-time impedance is compared to a standard deviation 2 of the average impedance value within a 1 second window. In another specific example, the real-time impedance may be compared to a fixed number (eg, determine if the standard deviation is greater than 10). In still other examples, other arrangements may be used.

  If the real-time impedance measurement is within this range, no message is displayed. However, if the real-time impedance is not within an average standard deviation of 2, the electrode may not be stable (ie, drifting, moving, etc.) and is described above with reference to FIGS. 10A and 10B. One or both of the message (s) (eg, “waiting for contrast agent to clear”, “electrode may be unstable”) may be displayed to the user. By way of example only, for contrast agent injection detection, in addition to the standard deviation of impedance, the algorithm is configured to take into account the standard deviation of real-time temperature measurements to look for real-time temperature excursions below the starting body temperature. May be. The exact value for truncation of temperature deviation may vary. In one particular example, if there is an impedance increase (eg, standard deviation> 10) that accompanies a decrease in real-time temperature, the system should be displayed to the operator “Contrast cleared. It is configured to flag a contrast agent detection event leading to a “wait for” message. In other examples, however, other algorithms and / or ranges may be used to determine contrast agent injection events and / or electrode stability. Further, in some embodiments, the system may modify / adjust various treatment parameters based on detected conditions without displaying such messages to the clinician.

IV. Related Anatomy and Physiology The following discussion provides further details regarding the related patient anatomy and physiology. This section is intended to supplement and expand the previous description of applicable anatomy and physiology, and provide additional context on the disclosed techniques and therapeutic benefits associated with renal denervation. Is done. For example, as already mentioned, some properties of the renal vasculature report the design of therapeutic devices and associated methods for achieving renal neuromodulation via intravascular access and are specific to such devices. May impose significant design requirements. Specific design requirements include access to the renal arteries, facilitating stable contact between the energy delivery elements of such devices and the luminal surface or wall of the renal arteries, and / or the kidney with a neuromodulator. It may include modulating the nerve effectively.

A. Sympathetic nervous system The sympathetic nervous system (SNS) is a branch of the autonomic nervous system, along with the enteric nervous system and the parasympathetic nervous system. This is always active at the basal level (called sympathetic tone) and becomes more active in the case of stress. Like other parts of the nervous system, the sympathetic nervous system operates through a series of interconnected neurons. Sympathetic neurons are often considered part of the peripheral nervous system (PNS), but many are in the central nervous system (CNS). Spinal sympathetic neurons (which are part of the CNS) communicate with peripheral sympathetic neurons through a series of sympathetic ganglia. Within the ganglia, spinal cord sympathetic neurons merge with peripheral sympathetic neurons through synapses. Spinal cord sympathetic neurons are therefore referred to as presynaptic (or prenodal) neurons, whereas peripheral sympathetic neurons are referred to as postsynaptic (or postnodal) neurons.

  At synapses within the sympathetic ganglion, sympathetic preganglionic neurons release acetylcholine, a chemical messenger that binds to and activates nicotinic acetylcholine receptors on postganglionic neurons. In response to this stimulus, post-node neurons primarily release noradrenaline (norepinephrine). Long-term activation can lead to the release of adrenaline from the adrenal medulla.

  When released, norepinephrine and epinephrine bind to adrenergic receptors on peripheral tissues. Binding to adrenergic receptors causes a neuronal and hormonal response. Physiological manifestations include pupil dilation, increased heart rate, occasional vomiting, and elevated blood pressure. Increased sweating is also thought to result from the binding of sweat gland cholinergic receptors.

  The sympathetic nervous system is responsible for up-regulating and down-regulating many homeostasis mechanisms in an organism. Fibers from the SNS innervate tissue in almost all organ systems and provide at least some regulation functions for various events such as pupil diameter, intestinal motility, and urine output. This response is also known as the body's sympathoadrenal response when prenode sympathetic fibers (but also all other sympathetic fibers) that terminate in the adrenal medulla secrete acetylcholine, which is adrenaline. (Epinephrine) secretion is activated and noradrenaline (norepinephrine) secretion is reduced to a lower extent. Thus, this response, acting primarily in the cardiovascular system, is transmitted directly through impulses transmitted through the sympathetic nervous system and indirectly through catecholamines secreted from the adrenal medulla.

  Science typically sees an SNS as an automatic regulation system, that is, one that operates without conscious thought intervention. Evolutionary theorists suggest that in early organisms, the sympathetic nervous system worked to maintain survival because the sympathetic nervous system is responsible for priming the body for action. An example of this priming is the moment before waking, when sympathetic outflow increases spontaneously in preparation for action.

1. Sympathetic Nerve Chain As shown in FIG. 11, the SNS provides a neural network that allows the brain to communicate with the body. The sympathetic nerve is thought to originate within the spinal column, toward the middle of the spinal cord in the intermediate lateral cell column (or lateral corner) starting at the first thoracic spinal cord and extending to the second or third lumbar spinal cord. SNS is said to have thoracolumbar outflow because its cells begin in the thorax and lumbar regions of the spinal cord. These nerve axons exit the spinal cord through the anterior fine root / anterior root. They pass near the spinal (sensory) ganglia, where they enter the anterior branch of the spinal nerve. However, unlike somatic innervation, they pass through white traffic branches that connect to either the vertebral (near the spine) or the prespinal (near the aortic branch) ganglia that extend beside the spine. Divide immediately.

  To reach the target organs and glands, axons should travel long distances within the body, and to achieve this, many axons pass their messages through synaptic transmission through a second Relay to cells. The end of the axon is connected to the dendrites of the second cell across the space and synapse. The first cell (pre-synaptic cell) sends a neurotransmitter across the synaptic cleft, where it activates the second cell (post-synaptic cell). The message is then taken to the final destination.

  In the SNS and other components of the peripheral nervous system, these synapses are made at sites called ganglia. The cells that send the fibers are called pre-node cells, while the cells from which the fibers leave the ganglion are called post-node cells. As described above, SNS pre-node cells are located between the first thoracic spinal cord (T1) and the third lumbar spinal cord (L3). Postnodal cells have their cell bodies in the ganglia and send their axons to the target organ or gland.

  Ganglia include not only the sympathetic trunk but also the cervical ganglion (upper, middle, and lower), which sends sympathetic fibers to the head and thoracic organs, and the celiac and mesenteric ganglia ( This sends sympathetic fibers to the gastrointestinal tract).

2. Renal innervation As FIG. 12 shows, the kidney is innervated by the renal plexus RP, which is closely associated with the renal arteries. The renal plexus RP is the autonomic plexus that surrounds the renal artery and is incorporated into the outer membrane of the renal artery. The renal plexus RP extends along the renal arteries until it reaches the kidney entity. Fibers that contribute to the renal plexus RP arise from the celiac ganglion, superior mesenteric ganglion, aortic renal artery ganglion, and aortic plexus. The renal plexus RP, also called the renal nerve, mainly consists of sympathetic nerve components. There is no (or at least very minimal) innervation of the renal parasympathetic nerves.

  The prenodal neuron cell body is located in the middle lateral cell column of the spinal cord. Prenodal axons pass through paravertebral ganglia (they are not synapses) and become the small visceral nerve, minimal visceral nerve, first lumbar visceral nerve, second lumbar visceral nerve, celiac ganglion, superior mesentery Move to ganglia and aorto-renal artery ganglia. Postnodal neuronal cell bodies exit the aortic renal artery ganglion to the celiac ganglion, superior mesenteric ganglion, and renal plexus RP, and are distributed in the renal vasculature.

3. Renal sympathetic nerve activity Messages travel in two directions through the SNS. Centrifugal messages can simultaneously trigger changes in different parts of the body. For example, the sympathetic nervous system accelerates the heartbeat, widens the bronchi, reduces colonic motility (movement), contracts blood vessels, increases esophageal peristalsis, pupil dilation, raised hair (bird skin), and sweat ( May cause sweating) and increase blood pressure. Afferent messages carry signals from various organs of the body and sensory receptors to other organs, particularly the brain.

  Hypertension, heart failure, and chronic kidney disease are some of the many disease states that result from chronic activation of the SNS, particularly the renal sympathetic nervous system. Chronic activation of SNS is a maladaptive response that drives the progression of these disease states. Pharmaceutical management of the renin-angiotensin-aldosterone system (RAAS) is a long-standing but somewhat inefficient approach to reduce SNS overactivity.

  As mentioned above, the renal sympathetic nervous system has been identified both as an experimental and a major cause of complex pathophysiology of hypertension, capacity overload conditions (such as heart failure), and progressive kidney disease in humans. Yes. Studies that employ radioactive tracer dilution to measure norepinephrine overflow from the kidney to plasma have been shown to increase renal norepinephrine (NE) in patients with essential hypertension, especially in young hypertensive subjects. ) Reveals spillover rate, which corresponds to increased NE spillover from the heart, consistent with the hemodynamic profile typically seen in early hypertension, and increased heart rate, cardiac output, and kidney Characterized by vascular resistance. It is now known that essential hypertension is usually neurological and often accompanies significant sympathetic nervous system overactivity.

  Activation of cardiorenal sympathetic nerve activity is even more pronounced in heart failure as evidenced by an excessive increase in NE overflow from the heart and kidney to plasma in this patient group. In line with this view is a strong negative prediction of total mortality and renal sympathetic nerve activation for heart transplantation in patients with congestive heart failure independent of total sympathetic activity, glomerular filtration rate, and left ventricular ejection fraction A recent proof of value. These findings support the view that treatment regimens designed to reduce renal sympathetic stimulation have the potential to improve the survival of patients with heart failure.

  Both chronic kidney disease and end-stage renal disease are characterized by increased sympathetic activation. In patients with end-stage renal disease, plasma levels of norepinephrine above average have been shown to be predictive of both overall death and death from cardiovascular disease. This is also true for patients suffering from diabetes or contrast nephropathy. There is strong evidence to suggest that sensory afferent signals originating from diseased kidneys are a major cause of initiating and sustaining increased central sympathetic outflow in this group of patients, including hypertension, left Promotes the occurrence of well-known adverse outcomes of chronic sympathetic overactivity such as ventricular hypertrophy, ventricular arrhythmias, sudden cardiac death, insulin resistance, diabetes, and metabolic syndrome.

(I) Renal sympathetic efferent activity The sympathetic nerve to the kidney terminates in blood vessels, paraglomerular devices, and tubules. Renal sympathetic stimulation causes increased renin secretion, increased sodium (Na ⁺ ) reabsorption, and decreased renal blood flow. These neuromodulatory components of renal function are significantly stimulated in disease states characterized by elevated sympathetic tone and clearly contribute to increased blood pressure in hypertensive patients. Decreased renal blood flow and glomerular filtration rate as a result of efferent stimulation of the renal sympathetic nerve is a progressive complication of chronic heart failure in a clinical process that typically changes with the patient's clinical condition and treatment It can be the cornerstone of loss of renal function in cardiorenal syndrome, which is renal dysfunction as a disease. Pharmacological strategies that prevent the consequences of efferent stimulation of the renal sympathetic nerve include centrally acting sympathetic blockers, beta blockers (intended to reduce renin secretion), angiotensin converting enzyme inhibitors and receptor antagonists. (Intended to block the activating action of angiotensin II and aldosterone as a result of renin secretion), and diuretics (intended to antagonize sodium and water retention via renal sympathetic nerves). However, current pharmacological strategies have significant limitations including limited effectiveness, compliance issues, side effects, and others.

(Ii) Renal sensory afferent nerve activity The kidney communicates with a unitary structure in the central nervous system via the renal sensory afferent nerve. Some forms of “renal injury” may induce activation of sensory afferent signals. For example, renal ischemia, stroke volume or decreased renal blood flow, or adenosine enzyme abundance can trigger activation of afferent neurocommunication. As shown in FIGS. 13A and 13B, this afferent communication may be from the kidney to the brain or from one kidney to the other (via the central nervous system). These afferent signals can be integrated into the central nerve, resulting in increased sympathetic outflow. This sympathetic drive is directed towards the kidneys, thereby activating RAAS and inducing increased renin secretion, sodium retention, stroke retention, and vasoconstriction. Central sympathetic overactivity also affects other organs and body structures innervated by sympathetic nerves, such as the heart and peripheral vasculature, resulting in the negative effects of sympathetic activation described, some of which Such embodiments also contribute to an increase in blood pressure.

  Physiology is therefore (i) modulation of tissue with efferent sympathetic nerves will reduce inappropriate renin secretion, salt retention, and decreased renal blood flow, and (ii) afferent sensory nerves. The accompanying tissue modulation suggests that the systemic contribution to hypertension and other disease states associated with increased central sympathetic tone through its posterior hypothalamic and its direct effects on the contralateral kidney will be reduced. In addition to the central antihypertensive effect of afferent renal denervation, a desirable reduction in central sympathetic outflow to organs innervated by various other sympathetic nerves such as the heart and vasculature is expected.

B. Additional clinical benefits of renal denervation As given above, renal denervation is associated with inadequate fluid retention in hypertension, metabolic syndrome, insulin resistance, diabetes, left ventricular hypertrophy, chronic end-stage renal disease, heart failure It is probably of value in the treatment of some clinical conditions characterized by increased total sympathetic activity, such as cardiorenal syndrome, and sudden death, especially renal sympathetic activity. Renal denervation may also be useful in treating other conditions associated with generalized sympathetic hypersensitivity, as a decrease in afferent nerve signals contributes to a systemic decrease in sympathetic tone / drive. Thus, renal denervation may also serve other organs and body structures innervated by sympathetic nerves, including those identified in FIG. For example, as noted above, a decrease in central sympathetic drive may reduce insulin resistance that afflicts people with metabolic syndrome and type II diabetes. Furthermore, osteoporotic patients can also be activated by sympathetic nerves and benefit from sympathetic drive down-regulation associated with renal denervation.

C. Achieving Intravascular Access to the Renal Artery According to the present technology, neuromodulation of the left and / or right renal plexus RP closely associated with the left and / or right renal artery may be achieved through intravascular access. . As FIG. 14A shows, blood moved by the contraction of the heart is carried by the aorta from the left ventricle of the heart. The aorta descends through the thorax and branches into the left and right renal arteries. Under the renal artery, the aorta branches in two into a left iliac artery and a right iliac artery. The left and right iliac arteries descend through the left and right legs, respectively, and join the left and right femoral arteries.

  As FIG. 14B shows, blood collects in the vein, returns to the heart, enters the iliac vein through the femoral vein, and enters the inferior vena cava. The inferior vena cava branches into the left and right renal veins. Above the renal veins, the inferior vena cava ascends and carries blood into the right atrium of the heart. From the right atrium, blood is pumped through the right ventricle into the lungs where it contains oxygen. From the lungs, oxygenated blood is carried into the left atrium. From the left atrium, oxygenated blood is carried by the left ventricle back to the aorta.

  As will be described in more detail later, the femoral artery may be accessed and inserted at the base of the femoral triangle just below the midpoint of the inguinal ligament. The catheter may be inserted percutaneously into the femoral artery through this access site, passed through the iliac and aortic arteries, and placed in either the left or right renal artery. This comprises intravascular pathways that provide minimally invasive access to the respective renal arteries and / or other renal blood vessels.

  The wrist, upper arm, and shoulder regions provide other places for introduction of the catheter into the arterial system. For example, catheterization of either radial artery, brachial artery, or axillary artery may be used when selected. Catheters introduced through these access points descend the descending aorta through the left subclavian artery (or through the right subclavian artery and brachiocephalic artery) using standard angiography techniques, through the aortic arch. May be passed through the renal artery.

D. Characteristics and characteristics of the renal vasculature Since neuromodulation of the left and / or right renal plexus RP may be achieved according to the present technology through intravascular access, the characteristics and characteristics of the renal vasculature may be There may be constraints and / or information on the design of the devices, systems, and methods to achieve. Some of these characteristics and features may include hypertension, chronic kidney disease, vascular disease, end-stage renal disease, insulin resistance, diabetes, metabolic syndrome, etc. across a patient population and / or within a particular patient May change in response to disease states such as These properties and characteristics as described herein may have support for treatment effectiveness and specific design of intravascular devices. Properties of interest may include, for example, material properties / mechanical properties, spatial properties, hydrodynamic properties / hemodynamic properties and / or thermodynamic properties.

  As already described, the catheter may be advanced percutaneously into either the left renal artery or the right renal artery via a minimally invasive intravascular route. However, minimally invasive renal artery access can be difficult, for example, renal arteries are often very serpentine compared to some other arteries that are routinely accessed using a catheter. Thus, it may be a relatively small diameter and / or may be a relatively short length. In addition, renal artery atherosclerosis is common in many patients, particularly those with cardiovascular disease. The anatomy of the renal arteries can also vary greatly from patient to patient, which makes minimally invasive access more difficult. For example, there may be significant patient-to-patient variation in relative tortuousness, diameter, length, and / or atherosclerotic plaque burden, and the take-off angle at which the renal artery branches from the aorta . Devices, systems, and methods for achieving renal neuromodulation via intravascular access are those of the renal artery anatomy and its changes across the patient population when minimally invasively accessing the renal artery. These and other aspects should be considered.

  In addition to making renal artery access difficult, the details of the renal anatomy also make it difficult to establish a stable contact between the device and the luminal surface or wall of the renal artery. When the neuromodulation device includes an energy delivery element such as an electrode, the consistent positioning force and proper contact force applied by the energy delivery element to the vessel wall is important for predictability. However, navigation is hampered by the narrow space within the renal artery as well as the tortuous nature of the artery. Furthermore, the establishment of consistent contact can cause these factors to cause large movements of the renal arteries relative to the aorta, and the cardiac cycle can cause the renal arteries to temporarily expand (ie pulsate the walls of the arteries). So that it is made difficult by patient movement, breathing, and / or the cardiac cycle.

  Even after accessing the renal arteries and smoothing stable contact between the neuromodulator and the luminal surface of the artery, the nerves in and around the outer arterial membrane can be routed through the neuromodulator. Should be safely modulated. Effective application of thermal therapy from within the renal arteries is not trivial given the potential clinical complications associated with such therapy. For example, the intima and media of the renal arteries are very vulnerable to thermal damage. As described in more detail below, the intima-media thickness that separates the vessel lumen from its adventitia indicates that the target renal nerve may be several millimeters away from the luminal surface of the artery. means. Enough to modulate the target renal nerve without overcooling or heating the vessel wall to the extent that the wall is frozen, dried, or otherwise potentially affected to an undesirable degree Energy should be delivered to or removed from the target kidney nerve. A potential clinical complication associated with excessive heating forms a thrombus from blood clots flowing through the artery. Given that this thrombus can cause renal infarction and irreversible damage to the kidney, thermal therapy from within the renal artery should be carefully applied. Thus, complex fluid dynamics and thermodynamic conditions present in the renal arteries during treatment, particularly conditions that can affect heat transfer dynamics at the treatment site, are energy (eg, heat to be heated) from within the renal arteries. Energy) and / or removing heat from the tissue (eg, thermal conditions for cooling).

  The neuromodulator should also be configured to allow adjustable positioning and repositioning of energy delivery elements within the renal arteries, as the location of treatment can also affect clinical efficacy It is. For example, if there is a possibility that the renal nerves are circumferentially spaced around the renal artery, one may attempt to apply full circumference therapy from within the renal artery. In some situations, a full circle injury that may result from continuous circumferential treatment may potentially be related to renal artery stenosis. Accordingly, it may be desirable to form more complex lesions along the longitudinal dimension of the renal artery via the mesh structure described herein and / or reposition the neuromodulator to multiple treatment locations. However, the advantages of providing circumferential ablation may outweigh the possibility or risk of renal artery stenosis may be alleviated in certain embodiments or in certain patients, Note that the goal may be to bring. In addition, the variable positioning and repositioning of the neuromodulator exists in a proximal branch vessel that leaves the main artery of the renal artery, making it difficult to treat in situations where the renal artery is particularly tortuous or at some location May prove useful in some cases. Manipulation of the device within the renal artery should also take into account the mechanical damage caused by the device to the renal artery. For example, movement of the device in the artery, such as by inserting, manipulating, or passing through a bend, can contribute to incision, perforation, intimal exposure, or disruption of the inner elastic membrane.

  Blood flow through the renal arteries may be temporarily occluded for a short time with or without minimal complications. However, occlusion over a significant amount of time should be avoided to prevent damage to the kidney, such as ischemia. It may be beneficial to avoid simultaneous occlusion, i.e., if occlusion is beneficial to the embodiment, limit the duration of occlusion to e.g. 2-5 minutes.

  (1) renal artery intervention, (2) consistent and stable positioning of therapeutic elements relative to the vessel wall, (3) effective application of treatment across the vessel wall, (4) treatment to allow multiple treatment locations Based on the issues described above, such as device positioning, potentially repositioning, and (5) avoidance of blood flow obstruction or limited duration, various independence of renal vasculature that may be of interest The properties made and dependent include, for example, (a) vessel diameter, vessel length, intima-media thickness, coefficient of friction, and tortuousness, (b) vessel wall extensibility, stiffness, and modulus, (C) peak systole, end diastolic blood flow rate, and mean systolic-diastolic peak blood flow rate, and mean / maximum volume blood flow, (d) specific heat capacity of blood and / or vessel wall, blood and / or Vessel wall thermal conductivity and / or vessel wall treatment Convective and / or radiative heat transfer of blood flow through the limb, (e) movement of the renal artery relative to the aorta induced by breathing, patient movement, and / or pulsatile blood flow, and (f) aorta Including the bifurcation angle of the renal arteries. These properties will be described in more detail with respect to the renal arteries. However, depending on the devices, systems, and methods used to achieve renal neuromodulation, these properties of the renal arteries can also guide and / or constrain design features.

As noted above, the device positioned within the renal artery should conform to the artery geometry. The renal artery vessel diameter, D _RA, is typically in the range of about 2-10 mm, with most patient populations having a D _RA of about 4 mm to about 8 mm, averaging about 6 mm. The renal artery vessel length L _RA between its mouth and its distal bifurcation at the aorta / renal artery junction is generally in the range of about 5-70 mm, with the majority of the patient population in the range of about 20-50 mm. Is within. Since the target renal plexus is incorporated into the adventitial artery of the renal artery, the combined intima-media thickness, IMT (ie, radially outward from the luminal surface of the artery to the adventitia that houses the target nerve structure) The distance) is also noteworthy and is generally in the range of about 0.5-2.5 mm with an average of about 1.5 mm. Although a certain depth of treatment is important to reach the target nerve fibers, the treatment is too deep to avoid non-target tissues and anatomy such as renal veins (eg, from the inner wall of the renal artery> 5mm) should not.

  An additional characteristic of the renal artery that may be of interest is the degree of kidney movement relative to the aorta induced by respiration and / or blood flow pulsatility. The patient's kidney, located at the distal end of the renal artery, can move as much as 4 inches toward the skull with respiratory excursion. This gives great motion to the renal arteries that connect the aorta to the kidneys, thereby allowing the neuromodulator to be rigid and flexible to maintain contact between the thermal treatment element and the vessel wall during the respiratory cycle. May require a unique balance of sex. Furthermore, the bifurcation angle between the renal arteries and the aorta can vary greatly between patients and can also change dynamically within the patient due to, for example, kidney movement. The branch angle may generally be in the range of about 30 ° to 135 °.

V. Conclusion The above detailed description of some embodiments of the technology is not intended to be exhaustive or to limit the technology to the precise form disclosed above. While specific embodiments and examples of the technology have been described above for purposes of illustration, various equivalent modifications are possible within the scope of the technology that would be recognized by one of ordinary skill in the art. For example, although the steps are presented in a given order, alternative embodiments may perform the steps in a different order. The various embodiments described herein may also be combined to provide further embodiments.

  From the foregoing, while specific embodiments of the technology have been described herein for purposes of illustration, in order to avoid unnecessarily obscuring the description of some embodiments of the technology, It will be understood that well-known structures and functions are not shown or described in detail. Where the context allows, singular or plural terms may also include plural or singular terms, respectively. For example, as noted above, much of the disclosure herein describes the energy delivery element 24 (eg, an electrode) in the singular, but this disclosure does not exclude more than one energy delivery element or electrode. I want you to understand.

  Further, the word “or” means “or” in such a list unless it is specifically limited to mean only a single item excluding other items in the list of two or more items. Is interpreted as including (a) any single item in the list, (b) all of the items in the list, or (c) any combination of items in the list. Should. Further, the term “comprising” is meant to include at least the listed feature (s) so that any larger number of the same features and / or other features of the additional type are not excluded. Used throughout. While specific embodiments have been described herein for purposes of illustration, it will be appreciated that various modifications may be made without departing from the technology. Further, although advantages associated with certain embodiments of the technology have been described in the context of these embodiments, other embodiments may also exhibit such advantages, and all embodiments are not necessarily subject to the technology. It is not necessary to exhibit these advantages within the scope of Accordingly, the disclosure and related techniques may encompass other embodiments that are not explicitly illustrated or described herein.

The present disclosure may be defined by one or more of the following supplementary notes.
1.
A system for renal neuromodulation,
A catheter comprising an elongate shaft having a proximal portion and a distal portion, the catheter comprising an energy delivery element configured to be positioned within a renal vessel;
An energy source coupled to the energy delivery element and configured to deliver energy via the energy delivery element to a target neural fiber proximate to the wall of the renal blood vessel;
With
The energy source is
Increasing energy delivery to a predetermined first power level over a first time period;
Maintaining energy delivery at the first power level for a second time period;
Increasing energy delivery to a second predetermined power level if the temperature value is below a preset threshold temperature after the second time period;
Comprising components configured as
The energy source further comprises:
Obtaining a treatment data set corresponding to a completed treatment performed using the catheter, the energy source, and the energy delivery element;
Evaluating the treatment data set against one or more criteria to determine whether the evaluation of the completed treatment may have been within a predetermined range;
Providing an indication as to whether the assessment of the completed treatment may have been within a predetermined range;
A system comprising components configured as follows.
2.
The treatment data set is a first treatment data set corresponding to a first completed treatment, and the system further comprises:
The first predetermined power level based at least in part on the evaluation of the first treatment data and the indicator as to whether the evaluation of the first completed treatment was within the predetermined range. Modifying the first time period, the second time period, and / or the second predetermined power level;
Using the modified first predetermined power level, the modified first time period, the modified second time period, and / or the modified second predetermined power level; 2 treatments,
Obtaining a second treatment data set corresponding to the second completed treatment;
The system of claim 1 configured as follows.
3.
The system of claim 1, wherein the treatment data set includes data related to one or more of temperature-based measurements, impedance-based measurements, blood flow-based measurements, or movement-based decisions.
4).
The treatment data set is a temperature change over a specified time, a maximum temperature, a maximum average temperature, a minimum temperature, a temperature at a predetermined or calculated time relative to a predetermined or calculated temperature, an average over a specified time Temperature, maximum blood flow, minimum blood flow, blood flow at a predetermined or calculated time relative to a predetermined or calculated blood flow, average blood flow over time, maximum impedance, minimum impedance, predetermined or calculated impedance The one or more measurements related to the impedance change for a predetermined or calculated time relative to the impedance, the impedance change over a specified time, or the temperature change over a specified time System.
5.
The energy delivery element includes a first energy delivery element, and the catheter further comprises a second energy delivery portion coupled to the energy source and configured to deliver energy to the target neural fiber;
The treatment data set is a first data set related to an impedance based measurement of the first energy delivery element and a second data set related to an impedance based measurement of the second energy delivery element. Comprising
The system according to appendix 1.
6).
The system of claim 5, wherein evaluating the treatment data set against one or more criteria comprises comparing the first data set to the second data set.
7).
The system of claim 1, wherein evaluating the treatment data set includes generating a score that is used to determine whether the completed treatment was successful.
8).
The system of claim 1, wherein evaluating the treatment data set comprises performing a linear discriminant analysis.
9.
The system of claim 8, wherein the linear discriminant analysis generates a score that is used to determine whether the completed treatment was successful.
10.
The system of claim 1, further comprising a display screen, wherein the provided indicator includes a message displayed on the display screen.
11.
Further comprising an impedance sensor for measuring the impedance of the treatment site or the electrode, wherein the energy source further tracks impedance measurements in real time over a selected time period, and the real time impedance measurements are displayed on the display screen The system of claim 10, wherein the system is configured to display.
12
A computer readable storage medium containing instructions, when executed by a computer,
Increasing energy delivery to an energy delivery element supported by a catheter, wherein the energy delivery is increased to a predetermined first power level over a first time period, wherein the energy delivery element is in a renal vessel of a human patient Positioned to deliver energy to target neural fibers in the vicinity of the wall; and
Maintaining energy delivery at the first power level for a second time period;
Increasing energy delivery to a second predetermined power level if the temperature value is lower than a preset threshold temperature after the second time period;
Obtaining a treatment data set corresponding to a completed treatment performed using the energy delivery element;
Evaluating the treatment data set against one or more criteria to determine whether the evaluation of the completed treatment may have been within a predetermined range;
Providing an indication as to whether the assessment of the completed therapy was within a predetermined range;
A computer-readable storage medium that performs operations including:
13.
The computer readable storage of claim 12, wherein the treatment data set includes data related to one or more of a temperature based measurement, an impedance based measurement, a blood flow based measurement, or a movement based determination. Medium.
14
The computer-readable storage medium of claim 12, wherein the operating parameter comprises one or more of temperature, time, impedance, power, blood flow, flow rate, volume flow rate, blood pressure, or heart rate.
15.
The treatment data set is a temperature change over a specified time, a maximum temperature, a maximum average temperature, a minimum temperature, a temperature at a predetermined or calculated time relative to a predetermined or calculated temperature, an average over a specified time Temperature, maximum blood flow, minimum blood flow, blood flow at a predetermined or calculated time relative to a predetermined or calculated blood flow, average blood flow over time, maximum impedance, minimum impedance, predetermined or calculated impedance 15. The one or more measurements related to the impedance change at a predetermined or calculated time relative to a change in impedance over a specified time, or a change in impedance over a specified time over temperature. Computer readable storage medium.
16.
The treatment data set includes a first treatment data set corresponding to a first completed treatment;
The first predetermined power level based at least in part on the evaluation of the first treatment data and the indicator as to whether the evaluation of the first completed treatment was within a predetermined range; Modifying the first time period, the second time period, and / or the second predetermined power level;
Using the modified first predetermined power level, the modified first time period, the modified second time period, and / or the modified second predetermined power level; Two treatments,
Obtaining a second treatment data set corresponding to a second completed treatment;
The computer-readable storage medium according to appendix 12, further comprising:
17.
Evaluating the treatment data set generates a score that is used to determine whether the completed treatment was within the predetermined range or whether the completed treatment did not proceed as expected. The computer-readable storage medium according to appendix 12, including:
18.
The computer readable storage medium of claim 12, wherein evaluating the treatment data set comprises performing a linear discriminant analysis.
19.
18. The computer readable storage medium of claim 17, wherein the linear discriminant analysis generates a score that is used to determine whether the completed treatment was within the predetermined range.
20.
13. The computer readable storage medium of claim 12, wherein the provided indication includes a message displayed on a display screen of a system used to deliver the completed treatment.
21.
Providing an indication as to whether the completed treatment was within the predetermined range;
Displaying a first message on the display screen when the treatment rating is within the predetermined range;
Displaying a second different message on the display screen when the evaluation of the therapy indicates that the therapy did not proceed as expected;
The computer-readable storage medium according to appendix 20, comprising:
22.
Increasing energy delivery to a predetermined second power level when the operating parameter is outside the predetermined range results in a difference in impedance values from the first energy delivery element and the second energy delivery element being within the predetermined range. 13. The computer readable storage medium of claim 12, comprising increasing energy delivery to a predetermined second power level when outside.

Claims (20)

A system for renal neuromodulation,
A catheter comprising an elongate shaft having a proximal portion and a distal portion, the catheter comprising an energy delivery element configured to be positioned within a renal vessel;
An energy source configured to couple to the energy delivery element and configured to deliver energy via the energy delivery element to a target neural fiber proximate to a wall of the renal vessel;
With
The energy source is
A first component for controlling energy delivery comprising:
Increasing energy delivery to a predetermined first power level over a first time period;
Maintaining energy delivery at the first power level for a second time period;
Increasing energy delivery to a second predetermined power level if the temperature value is below a preset threshold temperature after the second time period;
Comprising a first component characterized by being configured as follows:
The energy source further comprises:
A second component,
After the treatment cycle is complete,
Obtaining a treatment data set corresponding to a completed treatment cycle performed using the catheter, the energy source, and the energy delivery element;
Evaluating the treatment data set against one or more criteria to determine whether the evaluation of the completed treatment cycle may have been within a predetermined range;
Providing an indication as to whether the assessment of the completed treatment cycle may have been within a predetermined range;
Characterized in that it comprises a second component characterized by being configured as follows :
The treatment data set is a first treatment data set corresponding to a first completed treatment cycle, and the system further comprises:
The first predetermined power based at least in part on the evaluation of the first treatment data and the indicator as to whether the evaluation of the first completed treatment cycle was within the predetermined range. Modifying a level, the first time period, the second time period, and / or the second predetermined power level;
Using the modified first predetermined power level, the modified first time period, the modified second time period, and / or the modified second predetermined power level; 2 treatment cycles,
Obtaining a second treatment data set corresponding to a second completed treatment cycle;
A system characterized by being configured as follows .
The system of claim 1 wherein the treatment data set, characterized measurements for temperature, measurements of impedance, to include data related to one or more of the measures of blood flow.
The treatment data set is a temperature change over a specified time, a maximum temperature, a maximum average temperature, a minimum temperature, a temperature at a predetermined or calculated time relative to a predetermined or calculated temperature, an average over a specified time Temperature, maximum blood flow, minimum blood flow, blood flow at a predetermined or calculated time relative to a predetermined or calculated blood flow, average blood flow over time, maximum impedance, minimum impedance, predetermined or calculated impedance characterized in that it comprises a impedance, change in impedance over a specified time, or one or more measurements related impedance change with respect to the specified time over temperature change in predetermined or calculated time for The system of claim 1.
The energy delivery element includes a first energy delivery element, and the catheter further comprises a second energy delivery portion coupled to the energy source and configured to deliver energy to the target neural fiber;
The treatment data set is a first data set related to an impedance based measurement of the first energy delivery element and a second data set related to an impedance based measurement of the second energy delivery element. the system according to claim 1, characterized in that it comprises a.
5. The method of claim 4 , wherein evaluating the treatment data set against one or more criteria comprises comparing the first data set to the second data set. The described system.
The system of claim 1 wherein evaluating the therapeutic data set, which comprises generating a score used to determine whether the completed treatment cycle was successful.
The system of claim 1 to evaluate the therapeutic data set, characterized in that it comprises performing a linear discriminant analysis.
The system of claim 7, wherein the linear discriminant analysis, and generating a score used to determine whether the completed treatment cycle was successful.
The system of claim 1, further comprising a display screen, indicator said is provided, characterized in that it comprises a message displayed on the display screen.
Further comprising an impedance sensor for measuring the impedance of the treatment site or the electrode, wherein the energy source further tracks impedance measurements in real time over a selected time period, and the real-time impedance measurements are displayed on the display screen. the system of claim 9, wherein the configured to display on.
A computer readable storage medium containing instructions, when executed by a computer,
Increasing energy delivery to an energy delivery element supported by a catheter, wherein the energy delivery is increased to a predetermined first power level over a first time period, wherein the energy delivery element is in a renal vessel of a human patient Positioned to deliver energy to target neural fibers in the vicinity of the wall; and
Maintaining energy delivery at the first power level for a second time period;
Increasing energy delivery to a second predetermined power level if the temperature value is lower than a preset threshold temperature after the second time period;
Obtaining a treatment data set corresponding to a completed treatment cycle performed using the energy delivery element;
Evaluating the treatment data set against one or more criteria to determine whether the evaluation of the completed treatment cycle may have been within a predetermined range;
Providing an indication as to whether the evaluation of the completed treatment cycle was within a predetermined range;
It is characterized by performing operations including
The treatment data set includes a first treatment data set corresponding to a first completed treatment cycle;
The first predetermined power level based at least in part on the evaluation of the first treatment data and the indication as to whether the evaluation of the first completed treatment cycle was within a predetermined range. Modifying the first time period, the second time period, and / or the second predetermined power level;
Using the modified first predetermined power level, the modified first time period, the modified second time period, and / or the modified second predetermined power level; Performing two treatment cycles,
Obtaining a second treatment data set corresponding to a second completed treatment cycle;
A computer-readable storage medium further comprising:
It said treatment data set, the measurement of temperature based, impedance based measurement, computer-readable storage medium of claim 11, characterized in that it comprises data relating to one or more of the blood flow based measurements .
Said operating parameters, temperature, time, impedance, power, blood flow, flow rate, volume flow rate, the computer-readable medium according to claim 11, characterized in that it comprises a blood pressure, or one or more of the heart beat.
The treatment data set is a temperature change over a specified time, a maximum temperature, a maximum average temperature, a minimum temperature, a temperature at a predetermined or calculated time relative to a predetermined or calculated temperature, an average over a specified time Temperature, maximum blood flow, minimum blood flow, blood flow at a predetermined or calculated time relative to a predetermined or calculated blood flow, average blood flow over time, maximum impedance, minimum impedance, predetermined or calculated impedance characterized in that it comprises a impedance, change in impedance over a specified time, or one or more measurements related impedance change with respect to the specified time over temperature change in predetermined or calculated time for The computer-readable storage medium according to claim 11 .
Evaluating the treatment data set generates a score that is used to determine whether the completed treatment cycle was within the predetermined range or whether the completed treatment cycle did not proceed as expected. The computer-readable storage medium according to claim 11 , further comprising:
Wherein evaluating the therapeutic data set, a computer readable storage medium of claim 11, characterized in that it comprises performing a linear discriminant analysis.
The computer-readable storage medium of claim 15 linear discriminant analysis, the complete therapeutic cycle and generates a score that is used to determine whether the was within a predetermined range.
The computer-readable storage medium of claim 11, wherein the indicator is provided, characterized in that it comprises a message displayed on a display screen of the system used to apply the treatment cycle described above completed.
Providing an indication as to whether the completed treatment cycle was within the predetermined range;
Displaying a first message on the display screen when the evaluation of the completed treatment cycle is within the predetermined range;
Displaying a second different message on the display screen when an evaluation of the completed treatment cycle indicates that the treatment cycle has not progressed as expected;
The computer-readable storage medium of claim 18, characterized in that it comprises a.
Increasing energy delivery to a predetermined second power level when the operating parameter is outside the predetermined range results in a difference in impedance values from the first energy delivery element and the second energy delivery element being within the predetermined range. the computer-readable storage medium of claim 11, characterized in that it comprises increasing the energy delivered to a predetermined second power level if it is outside.

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